Selection of plasma donors for the production of anti-SARS-CoV-2 immunoglobulin-based therapies: Strategies for quantitative antibody measurements.

Even after two years of the pandemic, a completely effective treatment against SARS-CoV-2 has not yet been established. Considering this fact and the emergence of successive new viral variants, the development of therapies based on natural polyclonal antibodies recovered from convalescent plasma remains relevant. This study presents a comparison between different methods of screening antibodies in samples of 41 individuals previously diagnosed with COVID-19. We found a significant correlation between Abbot Architect anti-SARS-CoV-2 IgG and Abbott Allinity SARS-CoV-2 IgG II Quantitative assay intensity of reactivity and neutralizing antibody (nAb) titers. Thus, we propose an initial antibody screening with IgG anti-N Abbott Architect test, with an index of, for example, > 3.25 or SARS-CoV-2 IgG II Quantitative Abbott Allinity assay > 137.65 AU/mL as good predictors of Nab ≥ 1:80. For the quantitative method, this threshold demonstrated a 100 % sensitivity and 80 % specificity, with 97.3 % accuracy. An interesting observation was the increase in the neutralizing activity of the anti-SARS-CoV-2 antibodies with the longest interval between the end of the symptoms and the collection, demonstrating that the delay in plasma collection does not affect the achievement of adequate nAbs levels. These results demonstrate the possibility of using faster and more widely available commercial serological tests with a good correlation with viral neutralization tests in culture, allowing for optimized large-scale donor selection, which will be of utmost importance for the development of therapies such as hyperimmune immunoglobulin.

Revisiting old practices: More restricted indication of preoperative autologous blood donation in healthy bone marrow donors according to baseline hemoglobin levels.

There is no consensus on the risk-benefit status of preoperative autologous blood donation (PAD) for healthy bone marrow donors and there is concern regarding its impact on the development of pre-surgical anemia. We evaluated the changes in hemoglobin levels related to PAD in 80 bone marrow donors of our institution between 2002 and 2016. Mean Hgb values were compared separately for donors who donated 1 or 2 units, at 3 time-points: before PAD collection, the morning before marrow harvest and soon after harvest. Mean baseline Hgb values did not differ significantly between the 2 groups. After PAD collection, there was a significant drop in Hgb levels for the whole cohort of donors but more pronounced for the group that donated 2 units [1 unit: 12.8(8.9-17.4) × 2 units: 11.55(11.2-12.1), p = 0.045]. However, after marrow harvest, Hgb levels were similar for the 2 groups; 61.2% of all donors required autologous transfusion and none required allogeneic transfusion. Furthermore, baseline Hgb <14.35 g/dL was identified as the sensitive cutoff to predict the need for transfusion after marrow harvest (sensitivity of 52% and specificity of 80.4%, p = 0.001). Thus, our analysis demonstrates the possibility of using hemoglobin thresholds as cutoff points for indication of PAD, tending to a more cost-effective approach. Despite significant declines in Hgb levels after PAD, none of the donors in our cohort required allogeneic transfusion, demonstrating the safety of this procedure. Thus, the indication of PAD remains an option for those who feel insecure despite higher baseline Hgb levels.

The effects of exchange transfusion for prevention of complications during pregnancy of sickle hemoglobin C disease patients.

BACKGROUND: Pregnancy represents a challenge for women with sickle cell disease (SCD), with higher rates of both maternal and fetal complications. The aim of this study was to evaluate the impact of prophylactic transfusion support administered specifically to pregnant women with sickle hemoglobin C disease. MATERIALS AND METHODS: Patients were divided into two groups according to the type of transfusion support received: 10 women received prophylactic erythrocytapheresis or manual exchange transfusion at 28 weeks of gestation, and 14 received transfusions only on demand, due to acute complications, or received no transfusions at all. RESULTS: Our results indicated higher frequencies of SCD-related complications in the group that did not receive prophylactic transfusion support (35.7% vs. only 10% in the erythrocytapheresis group). Furthermore, these complications were more severe in this group and included all cases of acute chest syndrome. A significant difference was observed concerning gestational age at birth (38.7 weeks in the transfusion group vs. 34.4 weeks, p = 0.037), with a higher frequency of preterm births in the nontransfused group (69.23% vs. 30% in the transfusion group). CONCLUSION: We demonstrated a clear reduction of unfavorable outcomes in patients receiving prophylactic transfusions, probably reflecting better maternal and fetal conditions, which corroborated to the more satisfactory indices of vitality, observed in newborns. Considering that erythrocytapheresis or manual exchange transfusions both represent feasible and safe procedures, they could represent important tools for the optimal management of these patients.

Acupuncture as a Complementary Treatment for Leg Ulcers in Sickle-Cell Disease.

Background: Sickle-cell diseases (SCD) are a group of hereditary disorders in which a specific mutation in the gene that encodes the hemoglobin ß chain leads to formation of an anomalous hemoglobin molecule (HbS) with high polymerization power. This leads to sickling of erythrocytes in situations of low oxygen tension, such as in microcirculation, resulting in peripheral microvasculature occlusion, chronic hemolysis, inflammation, and damage to several target organs. Malleolar ulcers are among the most-debilitating complications of the disease, as they are associated with significant pain, secondary infections, and social impact due to their aesthetic impairment. There are no completely satisfactory therapeutic options for this complication; local healing agents, antibiotics, and dressings are used, with high rates of recurrence and complications, such as osteomyelitis and even limb amputation. Case: This case study evaluated the effect of Traditional Chinese Medicine techniques on chronic malleolar ulcers in a 49-year-old male patient. Ten sessions of systemic acupuncture (combinations involving Source, Master, Energetic Action, and Extraordinary Vessels points), auriculotherapy, and dressing with magnets were conducted. Results: Although the primary outcome sought was not reached (decrease in ulcer diameters), this patient had great reduction of local pain, a decrease in limb edema, and important reduction of his inflammatory condition, reflected in his decreasing blood levels of C-reactive protein. Conclusions: These results show that acupuncture should be considered as an important auxiliary treatment for SCD complications.

Consensus of the Brazilian association of hematology, hemotherapy and cellular therapy on patient blood management: Preoperative Clinical and Laboratory Assessment of the Patient.

The preoperative clinical and laboratory evaluations of the patient is an essential step to ensure the safety and success of any surgical procedure. This assessment aims to identify any underlying medical conditions and risk factors and determine suitability for surgery. With this step, the medical team can adapt the care plan to meet each patient's specific needs, increasing the chances of a successful procedure. Good clinical assessment and comprehensive laboratory testing, when integrated into a Patient Blood Management approach, are invaluable in promoting safety of care, reducing transfusion risks, improving surgical outcomes, and optimizing resource utilization. This approach not only elevates the quality of care, but is also aligned with evidence-based practice and patient-centered principles, making it an essential component of the perioperative process.

Consensus of the Brazilian association of hematology, hemotherapy and cellular therapy on patient blood management: Assessment and management of coagulation in the preoperative period.

Managing coagulation disorders and potential bleeding risks, especially in the context of anticoagulant medications, is of immense value both clinically and prior to surgery. Coagulation disorders can lead to bleeding complications, affecting patient safety and surgical outcomes. The use of Patient Blood Management protocols offers a comprehensive, evidence-based approach that effectively addresses these challenges. The problem is to find a delicate balance between preventing thromboembolic events (blood clots) and reducing the risk of bleeding. Anticoagulant medications, although crucial to preventing clot formation, can increase the potential for bleeding during surgical procedures. Patient blood management protocols aim to optimize patient outcomes by minimizing blood loss and unnecessary transfusions.

Consensus of the Brazilian association of hematology, hemotherapy and cellular therapy on patient blood management: Preoperative Phase - Preoperative management of the patient's anemia.

Managing anemia before surgery is extremely important as it is a clinical condition that can significantly increase surgical risk and affect patient outcomes. Anemia is characterized by a reduction in the number of red blood cells or hemoglobin levels leading to a lower oxygen-carrying capacity of the blood. Proper treatment requires a multifaceted approach to ensure patients are in the best possible condition for surgery and to minimize potential complications. The challenge is recognizing anemia early and implementing a timely intervention to correct it. Anemic patients are more susceptible to surgical complications such as increased infection rates, slower wound healing and increased risk of cardiovascular events during and after surgery. Additionally, anemia can exacerbate existing medical conditions, causing greater strain on organs and organ systems. To correct anemia and optimize patient outcomes, several essential measures must be taken with the most common being identifying and correcting iron deficiency.

Consensus of the Brazilian association of hematology, hemotherapy and cellular therapy on patient blood management: Anemia tolerance mechanisms.

Understanding the physiological concepts of oxygen delivery is essential to discern the mechanisms that influence its increase, reduction or maintenance in the body. This text explores the different mechanisms that help maintain oxygen delivery even in the face of reduced hemoglobin levels. Adequate oxygen delivery ensures tissue and metabolic balance, which is crucial to avoid harmful consequences such as metabolic acidosis and cellular dysoxia. The complex interaction between variables such as cardiac output, hemoglobin and heart rate (HR) plays a fundamental role in maintaining oxygen delivery, allowing the body to temporarily adjust to situations of anemia or high metabolic demand. It is important to emphasize that blood transfusions should not be based on fixed values, but rather on individual metabolic needs. Strategies to reduce myocardial consumption and monitor macro and micro hemodynamics help in making rational decisions. Individualizing treatment and considering factors such as blood viscosity in relation to the benefits of transfusion are increasingly relevant to optimize therapy and minimize risks, especially in complex clinical scenarios, such as neurocritical patients and trauma victims.

Consensus of the Brazilian association of hematology, hemotherapy and cellular therapy on patient blood management: Assessment and management of postoperative anemia.

Postoperative anemia is a complex clinical issue that requires attention due to its ramifications on the patient's recovery and prognosis. Originating from multiple determinants, such as intraoperative blood loss, hemolysis, nutritional deficiencies, systemic inflammation and impact on the bone marrow, postoperative anemia has varied and often challenging presentations. Patients undergoing major surgical procedures, in particular, are susceptible to developing anemia due to the considerable associated blood loss. Accurate diagnosis plays a crucial role in the approach, requiring meticulous hematological analysis, including hemoglobin, hematocrit and reticulocyte count, as well as an in-depth investigation of the underlying causes. An additional challenge arises in the form of the excessive practice of phlebotomy during hospitalization for clinical monitoring. Although it is essential to assess the progression of anemia, frequent removal of blood may contribute to iatrogenic anemia, further delaying recovery and possibly increasing susceptibility to infection.

Consensus of the Brazilian association of hematology, hemotherapy and cellular therapy on patient blood management: Anemia tolerance.

Anemia is a pathological condition in which the hemoglobin and red blood cell mass decrease; it is mainly defined by the concentration of hemoglobin in the blood. The World Health Organization guidelines establish specific values to define anemia in different population groups. Early detection of anemia can also be a valuable indicator of underlying medical conditions. Clinical studies have explored the relationship between perioperative anemia and morbidity, highlighting the need for more judicious therapeutic strategies, such as the use of Patient Blood Management, which aims to prevent and treat anemia in a personalized and effective way. Patient Blood Management emerges as a promising approach to dealing with anemia, recognizing that its correction through transfusion always carries risks and that personalized prevention and treatment can offer better outcomes for patients.

Prehospital blood transfusion in Brazil: results of the first year of implementation in an emergency medical service.

INTRODUCTION: Hemorrhagic shock is the main cause of death in the prehospital environment, which highlights the need to standardize measures aiming at bleeding control and volume replacement in this environment. In Brazil, the first prehospital packed red blood cell transfusion service started in September 2020, in Bragança Paulista, state of São Paulo. OBJECTIVES: Describe the trends and characteristics of patients who received prehospital transfusions prior to hospital treatment during the first year of operation. METHODS: A retrospective data review was made of all patients who received transfusions from the mobile intensive care unit in Bragança Paulista over one year. RESULTS: In this period, 19 patients were transfused. Since activation, the average response time was 20 min. The mean shock indexes before and after blood transfusion were 2.16 and 1.1, respectively. During the course of the 1st year of prehospital transfusions, no blood was wasted and there were no adverse effects. CONCLUSION: Introduction of the prehospital packed red blood cell transfusion service was successful, with significant improvement in hemodynamic parameters.

Production of dendritic cell vaccines using different methods with equivalent results: Implications for emerging centers.

INTRODUCTION: Dendritic cell (DC) vaccines have demonstrated good efficacy in preventing relapse and in increasing survival of patients affected by a variety of both solid and hematological tumors. Most protocols used to generate these cells involve the automated separation of peripheral blood monocytes from patients. This approach requires specialized equipment, which elevates the cost of this type of therapy, potentially limiting the widespread access to patients. METHOD: In this study, we compare the yield and quality of dendritic cells generated from monocytes and isolated by an automated method or by manual methods using gradient centrifugation. RESULTS: The results demonstrate the equivalence of the 3 methods in relation to the yield and final quality of the product, however with considerable differences between the costs of these procedures. In addition, this study also demonstrates the feasibility of the antigenic pulse with autologous tumor cell lysates, constituting a source of antigens, not only easily obtained and manipulated, but also specific to the patient's tumor. CONCLUSION: These findings may have important implications for emerging centers interested in using this medical approach and potentially increase the access of a greater number of patients to this therapeutic option.

Postdonation information during dengue outbreaks at a single blood center in Brazil: An ally against transfusion-transmitted infections.

BACKGROUND: Brazilian blood banks encourage donors to report postdonation information (PDI) regarding conditions that would lead to deferral in an attempt to retrieve distributed nonconforming blood. OBJECTIVES: This study evaluated the profile of donors reporting PDI, the impact on transfusion safety, and the possible impact on the discard of blood products. SUBJECTS AND METHODS: We analyzed 115 consecutive PDIs between May 2014 and July 2015, a period comprising two dengue-like syndrome (DLS) outbreaks. RESULTS: These PDIs accounted for 87,780 blood donations. The average time for PDIs since donation was 4 (0-23) days and 190 blood components were discarded. DLS accounted for 21.7% of the PDIs analyzed; 11 of the 23 samples tested were nucleic acid test (NAT) positive for dengue and 2 positive for Zika virus (ZIKV). Six of these PDIs were reported after blood components have been transfused: After NAT testing, one of these recipients was diagnosed with dengue and another one with ZIKV infection, both possible transfusions transmitted but without clinical consequences. CONCLUSION: The high number of recovered blood components due to PDI suggests that PDI remains a great ally in the fight against transfusion-transmitted infections and may be particularly useful during outbreaks of emerging potentially blood-borne pathogens.

Low SARS-CoV-2 seroprevalence in a cohort of Brazilian sickle cell disease patients: Possible effects of emphasis on social isolation for a population initially considered to be at very high risk.

Despite being initially considered at higher risk for severe COVID-19, sickle cell disease (SCD) patients have mostly presented clinical severity similar to the general population. As their vulnerability to become infected remains uncertain, we assessed the seroreactivity for SARS-CoV-2 to estimate the prevalence of infection and possible phenotypic and socioeconomic determinants for their contagion. Serologic evaluation was performed on 135 patients with an overall prevalence of 11%; positivity was associated with older age and use of public transportation. We speculate that social distancing instructions recommended by our clinic may have contributed to lower levels of infection, but potential protection factors need further investigation.

Rapid clinical recovery of a SARS-CoV-2 infected common variable immunodeficiency patient following the infusion of COVID-19 convalescent plasma.

BACKGROUND: Common variable immunodeficiency is the most prevalent symptomatic primary immunodeficiency in adults. Affected patients fail to mount an appropriate humoral response against community acquired infectious diseases and recent reports have provided data supporting the increased susceptibility of these patients to severe SARS-CoV-2 infections. In this context, the infusion of COVID-19 convalescent plasma could represent an effective therapeutic strategy. CASE PRESENTATION: 25-year old woman diagnosed with common variable immunodeficiency in 2013, developed severe COVID-19 that rapidly progressed to pneumonia presenting with multiple bilateral lung opacities that were both central and peripheral and presented as ground-glass and consolidation types involving all lobes, bilaterally. As blood oxygen saturation decayed and lung abnormalities were not responsive to large spectrum antibiotics and corticosteroids, patient was placed on mechanical ventilation and compassionate-use of approved COVID-19 convalescent donor plasma was introduced. The patient presented a rapid response to the approach and mechanical ventilation could be interrupted 24 h after first dose of COVID-19 convalescent donor plasma. As a whole, the patient received four doses of 200 mL convalescent plasma during a period of 6 days. There was rapid improvement of clinical status, with interruption of supplemental oxygen therapy after 6 days and reduction of lung abnormalities as evidence by sequential computed tomography scans. CONCLUSIONS: This is a single patient report that adds to other few reports on common variable immunodeficiency and agammaglobulinemia, suggesting that COVID-19 convalescent donor plasma could be a valuable therapeutic approach to treat patients affected by dysgammaglobulinemias and presenting severe COVID-19.

Increased expression of APAF-1 in low-risk myelodysplastic syndrome: a possible role in the pathophysiology of myelodysplasia.

OBJECTIVES: APAF-1 is a central component of the intrinsic pathway of apoptosis, where APAF-1 dysregulation results in the development of diverse human neoplasms. The aim of this study was to characterize the mRNA expression levels of APAF-1 transcripts in low-risk and high-risk MDS and to elucidate whether the expression levels of APAF-1 transcripts are modulated with increased apoptosis in CD34(+) MDS cells undergoing erythroid differentiation. METHODS: APAF-1 (NM_181861) expression was verified, by quantitative RT-PCR, in bone marrow aspirates from 33 patients with myelodysplastic syndromes (MDS), at the time of diagnosis, and in erythroid differentiation cultures from CD34(+) from normal donors and patients with MDS. RESULTS: APAF-1 expression was significantly higher in low-risk, compared to high-risk MDS, according to IPSS (P < 0.0001), FAB (P = 0.0265), and cytogenetic risk (P = 0.0134). Low-risk MDS-derived differentiated erythroid cells demonstrated an increased expression of APAF-1, compared with normal cells, accompanied by an augmented rate of apoptosis. CONCLUSIONS: Increased expression of APAF-1 in low-risk disease and its positive correlation with the apoptotic rate observed during the erythroblast differentiation of low-risk MDS cells may indicate that the modulation of APAF-1, at the transcriptional level, participates in the pathophysiology of MDS.

An update on arginine in sickle cell disease.

INTRODUCTION: Recent knowledge on the pathophysiology of sickle cell disease (SCD) have emphasized the role of hemolysis and nitric oxide (NO) depletion on the occurrence of acute and chronic complications. This new paradigm raises the possibility of innovative therapeutic approaches, including arginine supplementation. Areas covered: This review comments on the role of NO in the regulation of vascular tone, as well as its impaired metabolism in hemolytic diseases. Disturbances in these processes in SCD were detailed considering the functions of endothelial nitric oxide synthase (eNOS), arginase and asymmetric dimethylarginine (ADMA). Therapeutic approaches involving these pathways were discussed with emphasis on the effects of arginine therapy on the normalization of NO levels and its consequent clinical effects, mainly the decrease in the intensity of vaso-occlusive crises. Expert opinion: Considering the complex pathogenesis of the disease and the restricted access to curative therapies, the management of SCD must rely on a combination of therapies covering multiple pathways. Arginine supplementation, a low-cost approach, has shown promising results, which is particulary important considering most of the affected patients still live in unfavorable socioeconomic conditions. These findings should encourage further clinical trials, evaluating other outcomes and specific subpopulations, such as adult patients and compound heterozygotes.

Small Particles, Big Effects: The Interplay Between Exosomes and Dendritic Cells in Antitumor Immunity and Immunotherapy.

Dendritic cells play a fundamental role in the antitumor immunity cycle, and the loss of their antigen-presenting function is a recognized mechanism of tumor evasion. We have recently demonstrated the effect of exosomes extracted from serum of patients with acute myeloid leukemia as important inducers of dendritic cell immunotolerance, and several other works have recently demonstrated the effects of these nanoparticles on immunity to other tumor types as well. The aim of this review was to highlight the recent findings on the effects of tumor exosomes on dendritic cell functions, the mechanisms by which they can lead to tumor evasion, and their manipulation as a possible strategy in cancer treatment.